Antibiotics: Chemotherapy and Principal Classes

Antibiotics are chemical substances produced by microorganisms that have the capacity, at low concentrations, to kill or inhibit the growth of other microorganisms. To date, about 10,000 antibiotics have been isolated and described and the chemical structure of the majority has been determined.

Chemically, antibiotics are a very diverse group. Their molecules may contain only carbon and hydrogen, or, more commonly, carbon, hydrogen, oxygen, and nitrogen; pthers also contain phosphorus, sulfur, or halogen atoms. The only property that all antibiotics have in common is that they are organic solids.

Microorganisms Producing Antibiotics

This large variety of molecules is produced by an array of widely diverse microorganisms. More than 50% of known antibiotics are produced by members of only one bacterial order, Actinomycetales, and particularly by one genus of this order, Streptomyces. Only two genera of fungi, Aspergillus and Penicillium, produce a relatively high number of antibiotics. The same antibiotic can be produced by organisms belonging to different species or even orders. And the reverse is also true; that is same species can produce different antibiotics.

Mechanism of Action

Antibiotics block the growth of sensitive microorganisms by inhibiting the action of a molecule, such as an enzyme or nucleic acid, essential for cell multiplication.

Chemotherapy

Although about 10,000 have been isolated, and tens of thousands of compounds have been synthesized chemically and tested for their antimicrobial activity, only a few have been found to possess the characteristics necessary for clinical use:

  • Activity against one or more disease-causing (pathogenic) microorganisms.
  • Good absorption and distribution.
  • Lack of toxicity.

Principal Classes of Antibiotics

Various schemes for classification of antibiotics have been proposed, none of which have been universally adopted. Currently, those natural or semisynthetic antibiotics that have a common basic chemical structure are grouped into one class and named after the member first discovered or after a principal chemical property.

β-Lactam Antibiotics (Penicillins and Cephalosporin)

This group of antibiotics is so called because of the presence in their molecule of a four-atom cyclic amide, chemically called β-lactam. The β-lactam antibiotics inhibit the synthesis of peptidoglycan, a basic component of the bacterial cell wall, causing irreversible damage. Their toxicity, in general, is very low.

Tetracyclins

This group is characterized by its very broad spectrum of action and great therapeutic effectiveness. The tetracyclins are products of different strains of Streptomyces. Tetracyclins act by preventing ribosomal protein synthesis. The effect is reversible and, therefore, they are bacteriostatic agents.

Aminoglycoside Antibiotics

These form a large class of substances produced by members of the genera Streptomyces, Micromonospora, and Bacillus. They are characterized chemically by the presence of a cyclic amino alcohol to which some amino sugars are bound. The aminoglycoside antibiotic inhibit protein synthesis irreversibly by interacting with ribosomes, which leads to bacterial cell death. These antibiotics are particularly active against gram-negative bacteria.

Macrolides

The chemical structure of these antibiotics is characterized by a ring consisting of no fewer than 12 carbon atoms and closed by a lactone group. They are typical products of Streptomyces. The macrolides are subdivided into two classes: antibacterial macrolides and antifungal and antiprotozoal macrolides.

Ansamycins

Ansamycins are produced by members of several genera of the order Actinomycetales. Ansamycins are subdivided into two groups, the naphthalenes and the benzenes.

Peptide Antibiotics

Peptide antibiotics are produced by a great variety of microorganisms. Among the peptide used systematically are the polymyxins, which are very effective against gram-negative bacteria.

Glycopeptide Antibiotics

The important members of this class are vancomycin and teicoplanin, which are active against gram-positive bacteria, in particular staphylococci resistant to β-lactam antibiotics.

Antitumor Antibiotics

These belong to different chemical classes but all act on DNA replication by different mechanisms, such as breakage of DNA filaments.

Some antibiotics used in therapy cannot be classified in any of the families. Some of these are chloramphenicol, lincomycin, novobiocin, fusidic acid, fosfomycin, griseofulvin, and mupirocin. (Adapted from Antibiotics: a multidisciplinary approach. Giancarlo Lancini, Francesco Parenti, Gian Gualberto Gallo.)